Nelson's syndrome classically presents with a pronounced pigmentation of the skin due to high levels of ACTH and melanocyte stimulating hormone. This is associated with a large, invasively growing tumour of the pituitary that occurs in up to 20% of those who have had a bilateral adrenalectomy.
When the adrenal glands have been removed, there is very little cortisol circulating, hence there is less negative feedback to the pituitary gland. This causes an increased cleavage of Pro-Opiomelanocortin (POMC) to ACTH and melanocyte stimulating hormone (MSH), the latter responsible for increasing skin pigmentation (see physiology section for a reminder of how the system works). This is becoming rarer due to the decrease in adrenalectomies performed. External radiation immediately after surgery is thought to prevent Nelson's syndrome.